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Blood, Vol. 110, Issue 9, 3281-3290, November 1, 2007

Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma
Blood Kuhn et al.
110: 3281
Supplemental materials for: Kuhn et al
Files in this Data Supplement:
- Figure 1. Carfilzomib’s activity in resistant cell lines (PDF, 19.8 KB) -
(A), Inhibition of proliferation in ANBL-6 wild type (ANBL-6.wt) and bortezomib-resistant (ANBL-6.BR) cells treated with 1, 5, or 10 nM bortezomib continuously for 24 hours. RPMI8226.BR (B) and OPM-2.BR (C) cells, along with their wild type counterparts, were pulsed with carfilzomib for 1 hour, and proliferation was assessed using the colorimetric WST-1 reagent after a 24 hour recovery period. The degree of resistance (D.O.R.) to bortezomib was computed by comparing the IC50’s of bortezomib-sensitive and -resistant cells. (D) Representative original data showing carfilzomib’s activity in wild type (8226.wt) and doxorubicin-resistant (8226.Dox40) myeloma cells in the presence or absence of the p-glycoprotein inhibitor verapamil (15 µM) for 24 hours, followed by a 1 hour pulse with increasing concentrations of carfilzomib. Cytotoxicity was assessed 24 hours later using the WST-1 reagent.
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